Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MICROGLIAL CELL EXPRESSION OF THE TYPE 2 CANNABINOID RECEPTOR REGULATES IMMUNE-MEDIATED NEUROINFLAMMATION

ABSTRACT: Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells and inflammatory cytokines play a role in this process, the precise interplay between the adaptive and innate arms of the immune system that propagates inflammation in the central nervous system remains incompletely understood. Using a murine model of GVHD, we demonstrate that type 2 cannabinoid receptor (CB2R) signaling plays a critical role in the pathophysiology of neuroinflammation. In these studies, we identify that CB2R expression on microglial cells induces an activated inflammatory phenotype which potentiates the accumulation of donor-derived proinflammatory T cells, regulates chemokine gene regulatory networks, and promotes neuronal cell death. Pharmacological targeting of this receptor with a brain penetrant CB2R inverse agonist/antagonist selectively reduced neuroinflammation without deleteriously affecting systemic GVHD severity. Thus, these findings delineate a therapeutically targetable neuroinflammatory pathway and has implications for the attenuation of neurotoxicity after GVHD and potentially other T cell-based immunotherapeutic approaches.

ORGANISM(S): Mus musculus

PROVIDER: GSE252964 | GEO | 2024/05/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model.

Project description:Several studies have indicated that the cannabinoid receptor 2(CB2) plays an important role in neuroinflammation associated with Alzheimer’s disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model ofAD (APP/PS1mice). We demonstrate that microglia harvested from CB2-/- mice were less responsive to pro-inflammatory stimuli than CB2+/+ microglia based on the cell surface expression of ICAM and CD40 and the release of chemokines and cytokines CCL2, IL-6, and TNFα. Transgenic APP/PS1 mice lacking CB2showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokine in the brain, as well as diminished concentrations of soluble Aβ 40/42.The reduction in neuroinflammation did not affect spatial learning and memory in APP/PS1*CB2-/- mice. These data suggest a role for the CB2 in Alzheimer’s disease-associated neuroinflammation independent of influencing Aβ mediated pathology and cognitive impairment.

2017-01-09 | GSE60903 | GEO

Cannabinoid receptor type 2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions [snRNA-seq]

Project description:Since its detection in the brain, the cannabinoid receptor type 2 (CB2) has been considered a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of its expression is still lacking. Using magnetic cell sorting, calibrated RT-qPCR and single-nucleus RNAseq, we show that CB2 is expressed at a low level in all brain regions studied, mainly by few microglial cells, and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation, modeling neuroinflammation in non-sterile conditions, we demonstrate that the inflammatory response is associated with a transient reduction in CB2 mRNA levels in brain tissue, particularly in microglial cells. This result, confirmed in the BV2 microglial cell line, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, modeling neuroinflammation in sterile condition. Discrete brain CB2 expression might thus be up- or down-regulated depending on the inflammatory context.

2024-08-25 | GSE247268 | GEO

The cannabinoid agonist WIN55,212-2 (WIN) suppresses the inflammation-associated transcriptional response of astrocytes to interleukin 1 beta

Project description:Accumulating evidence suggest that the endocannabinoid system is an attractive target to attenuate inflammatory responses that are implicated in neurodegeneration. Alterations in astrocytic functions play a crucial role in neuroinflammation as a consequence of the loss of their neuroprotective role or the gain of their toxic inflammatory properties. In this study, we explore the possible immunosuppressive action of the cannabinoid receptor agonist WIN55,212-2 using an in vitro model of primary human astrocytes that are activated by the pro-inflammatory cytokine interleukin 1 beta (IL1B). Genome-wide transcriptomic analysis using RNA-seq revealed that the pretreatment of astrocytic cultures with WIN55, 212-2 prevents the transcriptional activation of pro-inflammatory genes induced by IL1B. We report the immunosuppressive function of WIN55,212-2 in replicates RNA samples that were extracted from human astrocyte cultures established from one donor.

2021-01-01 | GSE160092 | GEO

Cannabinoid Receptor 1 Dependent Effects of Isopropoyl dodeycl fluorophosphonate on Hepatic Gene Expression

Project description:We tested the effects of isopropoyl dodecyl fluorophosphonate (IDFP) (10 mg/kg, i.p.), a pharmacological inhibitor of endocannabinoid degradation, on hepatic gene expression in mice. To determine if increased cannabinoid receptor 1 signaling is responsible for IDFP induced effects a subset of mice were pretreated with the cannabinoid receptor 1 antagonist (AM251) (10 mg/kg, i.p.). Total RNA obtained from liver of mice treated with DMSO (n=6), IDFP (n=8), or AM251/IDFP (n=5) (all 10 mg/kg i.p.) for 4 hours.

2011-09-30 | E-GEOD-22949 | biostudies-arrayexpress

MICROGLIAL CELL EXPRESSION OF THE TYPE 2 CANNABINOID RECEPTOR REGULATES IMMUNE-MEDIATED NEUROINFLAMMATION

Project description:MICROGLIAL CELL EXPRESSION OF THE TYPE 2 CANNABINOID RECEPTOR REGULATES IMMUNE-MEDIATED NEUROINFLAMMATION

| PRJNA1063329 | ENA

Cannabinoid Receptor 1 Dependent Effects of Isopropoyl dodeycl fluorophosphonate on Hepatic Gene Expression

2011-10-01 | GSE22949 | GEO

Cannabinoid Receptor 2 Agonists Attenuate HIV Replication and Inflammatory Activation in HIV-infected Myeloid Cells

Project description:Emerging evidence suggests brain-resident myeloid cells, including macrophages and microglia, provide a reservoir for HIV infection in the central nervous system (CNS), and their inflammatory activation is a proposed pathogenic mechanism in HIV-associated neurocognitive disorders (HAND). We investigated whether cannabinoid receptor 2 (CB2), an immunomodulatory receptor expressed in myeloid cells, regulates viral replication and inflammation in HIV-infected macrophages and microglia. Using the synthetic CB2-specific agonist, JWH-133, we found that CB2 activation reduces HIV replication in primary human monocyte-derived macrophages (MDMs) and human iPSC-derived microglia (iMg) at differing doses, corresponding to the basal expression of CNR2 and related endocannabinoid transcripts in each cell type. Direct CB2 agonism via JWH-133 broadly reduced cytokine release from HIV-infected MDMs, but not iMg. RNA-seq revealed that CB2 agonism primarily altered interferon and integrated stress response pathways in MDMs; homeostatic pathways, including synapse maintenance and phagocytosis, were altered in iMg. Further investigation in iMg found NLRP3 inflammasome activation, but not priming, was reduced by CB2 activation. This study identifies key discrepancies in CB2 response between myeloid cell types and implicates CB2-specific agonists as promising candidates for regulation of HIV-associated neuroinflammation.

2025-01-22 | GSE250616 | GEO

Modulating Cannabinoid CB1 Receptor as a Therapeutic Strategy for Cognitive Impairment Following Cerebral Ischemia

Project description:Cerebral ischemia, commonly resulting from an ischemic stroke, can lead to significant cognitive impairments due to neuronal damage and neuroinflammation. The cannabinoid CB1 receptor, part of the endocannabinoid system, plays a crucial role in modulating synaptic plasticity, neurogenesis, and neuroprotection. Research suggests that targeting the CB1 receptor could offer a promising therapeutic strategy to mitigate cognitive deficits following cerebral ischemia. Modulating CB1 receptor activity, either through agonists or antagonists, has been shown to influence key pathways involved in neuroprotection and inflammation, potentially enhancing recovery of cognitive functions. Understanding the mechanisms by which CB1 receptor modulation affects brain recovery post-ischemia could pave the way for novel treatments aimed at reducing the long-term cognitive impact of ischemic strokes.

2024-07-07 | PXD053731 |

Role of myeloid cannabinoid CB1 receptor in atherosclerosis

Project description:Role of myeloid cannabinoid CB1 receptor in atherosclerosis

| PRJNA1049407 | ENA

Role of myeloid cannabinoid CB1 receptor in atherosclerosis

Project description:Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cellspecific effects in this disease are not well understood. Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1 deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sexspecific differences in proliferation were dependent on estrogen receptor (ER)α estradiol signaling. Kinase activity profiling revealed a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further unveiled chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, hinting to a possible implication of CB1-dependent regulation in human pathophysiology. In conclusion, impaired macrophage CB1 signaling is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming. The importance of macrophage CB1 signaling seems to be more pronounced in male mice.

2023-12-07 | GSE249503 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data